Method for the treatment of consciousness disorders

Abstract

The present invention provides a method for the treatment of consciousness disorder comprising the steps of positioning at least two electrodes on a patient's head such that the first electrode is positioned on the right supraorbicular cortex and the second electrode is positioned on the left dorso-lateral prefrontal cortex; connecting said electrodes to at least one source of electrical current; delivering direct current to the electrodes, and removing the electrodes from the patient's head after a time T; wherein steps a) to d) represent a treatment session and wherein at least one treatment session is is applied on the patient's head at least 2 days per week.

Claims

1. A method for the treatment of a consciousness disorder comprising: a) positioning at least two electrodes on a patient's head such that the first electrode is positioned over the right supraorbicular cortex and the second electrode is positioned over the left dorso-lateral prefrontal cortex; b) connecting said electrodes to at least one source of electrical current; c) delivering direct current to the electrode, wherein an intensity of the direct current increases progressively during a period of time T, wherein T is at least 1 second and at most 5 minutes, and d) removing the electrodes from the patient's head after a time T; wherein a) to d) represent a treatment session and wherein at least one treatment session is applied on the patient's head at least 2 days per week.

2. The method according to claim 1 wherein one treatment session is applied at least one time every 24 hours.

3. The method according to claim 1, wherein the time T in step d) is at least 5 minutes.

4. The method according to claim 1, wherein the time T in step d) is at most 30 minutes.

5. The method according to claim 1, wherein an intensity of the direct current is from 0.5 to 3 mA.

6. The method according to claim 1, wherein an intensity of the direct current is about 2 mA.

7. The method according to claim 1, wherein the progressive increase of the direct current follows a slope of from 0.06 mA/sec to 0.6 mA/sec.

8. The method according to claim 1, wherein T is 5 seconds.

9. The method according to claim 1, wherein a density of the direct current is from 0 to 100 A/cm.sup.2.

10. The method according to claim 9, wherein the density of the direct current is from 50 to 60 A/cm.sup.2.

11. The method according to claim 1, wherein the treatment is applied during at least one week.

Description

DESCRIPTION OF THE FIGURES

(1) FIG. 1 shows time scale of the applied treatment and the CRS-R measurements.

(2) FIG. 2 shows the effect of the method of the invention on patient having MCS (i.e., the evolution of the CRS-R measurements for both type of treatment).

DETAILED DESCRIPTION OF THE INVENTION

(3) The present invention relates to a non-invasive method for the treatment of consciousness disorder. The method uses transcranial current stimulation for said treatment.

(4) As used herein, the following terms have the following meanings:

(5) A, an, and the as used herein refers to both singular and plural referents unless the context clearly dictates otherwise. By way of example, a compartment refers to one or more than one compartment.

(6) About as used herein referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of +/20% or less, preferably +/10% or less, more preferably +/5% or less, even more preferably +/1% or less, and still more preferably +/0.1% or less of and from the specified value, in so far such variations are appropriate to perform in the disclosed invention. However, it is to be understood that the value to which the modifier about refers is itself also specifically disclosed.

(7) Comprise, comprising, and comprises and comprised of as used herein are synonymous with include, including, includes or contain, containing, contains and are inclusive or open-ended terms that specifies the presence of what follows e.g. component and do not exclude or preclude the presence of additional, non-recited components, features, element, members, steps, known in the art or disclosed therein.

(8) The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within that range, as well as the recited endpoints.

(9) In a first aspect, the present invention provides a method for the treatment of consciousness disorder comprising the steps of:

(10) a) positioning at least two electrodes on a patient's head such that the first electrode is positioned on the right supraorbicular cortex and the second electrode is positioned on the left dorso-lateral prefrontal cortex;

(11) b) connecting said electrodes to at least one source of electrical current;

(12) c) delivering direct current to the electrodes, and

(13) d) removing the electrodes from the patient's head after a time T;

(14) wherein steps a) to d) represent a treatment session and wherein at least one treatment session is is applied on the patient's head at least 2 days per week.

(15) In a preferred embodiment, one treatment session is applied at least one time every 24 hours 7 days per week, preferably for maximum 6 days per week, more preferably for maximum 5 days per week. The treatment sessions can be applied at any time of the day and are preferably applied in the morning so between 6 am and 12 am. In a preferred embodiment, the repetitive treatment sessions are applied to the patient at the same time. For instance, if the first session has been applied on Monday at 10 am, the next session is to be applied on Tuesday at 10 am.

(16) Preferably, the time T in step d) is at least 5 minutes and at most 30 minutes, preferably at least 10 min and at most 20 min.

(17) The intensity of the direct current is of from 0.5 to 3 mA, preferably of from 1 to 2.5 mA, more preferably about 2 mA.

(18) Preferably, the intensity of the direct current increases progressively following a slope of from 0.06 mA/sec to 0.6 mA/sec, more preferably about 0.4 mA/sec. The intensity of the direct current increases progressively during a period of time T wherein T is at least 1 second and at most 5 minutes, preferably T is about 5 seconds.

(19) Preferably the density of the direct current is of from 0 to 100 A/cm.sup.2, preferably of from 50 to 60 A/cm.sup.2.

(20) The treatment is applied during at least one week and at most 10 weeks, preferably at least at least 2 weeks and at most 9 weeks, more preferably at least 3 weeks and at most 8 weeks, even more preferably at least 4 weeks and at most 7 weeks, most preferably at least 5 weeks and at most 6 weeks. The treatment can also be applied for several months or several years.

EXAMPLES

(21) Patients

(22) A group of traumatic and non-traumatic patients in a sub-acute and chronic MSC for at least 3 months has been selected for the treatment. The group consisted of 16 patients and comprised a mix of male and female patients of different age but of at least 18 years old. Patients with a metallic cerebral implant or a pacemaker were excluded from the group. Also patients who received a drug treatment and/or suffering from other disorders, such as epilepsy, were excluded from the group.

(23) Treatment

(24) One treatment session consisted of positioning two electrodes on the skull of the patient. The cathode was positioned above the right eyebrows and more exactly on the right supraorbicular cortex (FP2). The anode was positioned on the left dorso-lateral prefrontal cortex (F3). The electrodes were connected to an electric current generator. Direct current having an intensity of 2 mA and a density of from 50 to 60 A/cm.sup.2 was delivered to the patients for 20 min. The increase in current intensity was gradual following a slope of 0.4 mA/s.

(25) The above described treatment session has been repeated every day at the same time for 5 days per week.

(26) Each patient received, in a random order, the above treatment for 4 weeks and a placebo treatment for 4 weeks. The placebo treatment was made of a similar setup as the real treatment, but the stimulation was only active for 5 seconds. For the rest of the 20 minutes, no direct current was delivered by the placebo treatment. The two 4-week treatments were separated by a 8-week period without treatment. The treatment was applied either by the family at home, or by a nurse in a rehab center. The caregiver was blinded on the treatment.

(27) Results Measurement and Analysis

(28) Treatment result was assessed based on Coma Recovery Scale Revised (CRS-R) as described in Giacino et al., 2004, Arch Phys Med Rehabil. The measurements were performed on each patient before the treatment (Baseline A, FIG. 1), immediately after the treatment A (Post A, FIG. 1), 8 weeks after the end of the treatment A, which corresponds to the beginning of treatment B (Post 8w A=Baseline B, FIG. 1), immediately after the treatment B (Post B, FIG. 1) and 8 weeks after the end of treatment B (Post 8w B, FIG. 1). As mentioned earlier, patients were randomly assigned either real treatment or placebo treatment as treatment A, and the other as treatment B.

(29) The mean delta between Baseline and Post CRS-R score is +1.442.19 (statistically significant, p<0.05) for the real treatment and 0.132.25 (p>0.80) for the placebo treatment. The difference of this delta between the real treatment and the placebo treatment is also statistically significant (p<0.05).

(30) At the individual level, 10 out of 16 patients, i.e. 62.5% of the patients, showed a tDCS-related improvement. This is better than with a single session where the improvement observed in only 43% of the patient (reported in Thibaut et al. 2014). Repeating the stimulation increases patient's reactivity to the treatment.

(31) Although the present invention has been described with reference to preferred embodiments thereof, many modifications and alternations may be made by a person having ordinary skill in the art without departing from the scope of this invention which is defined by the appended claims.